Perivascular Inflammatory Cell Infiltration Research Articles

A Young Man With Hereditary Motor And Sensory Neuropathy: A Rare Genetic Association

Hereditary motor and sensory neuropathies with early onset are uncommon conditions that include Dejerine-Sottas neuropathy, which begins in infancy, and congenital hypomyelinating neuropathy, which manifests in the early postnatal period. However, these two historically defined disease entities are only small parts of the clinical spectrum. It is well recognized that very early onset hereditary neuropathies are frequently caused by de novo dominant mutations in PMP22, MPZ, and EGR2. In addition, mutations in several other dominant and recessive genes for Charcot-Marie-Tooth disease may lead to similar phenotypes. A 20-year-old boy had complaints of weakness of both lower limbs for 1 year, followed by wasting and foot drop, which subsequently involved the upper limbs. Nerve conduction velocity and electromyography of both lower limbs revealed demyelinating sensory motor polyneuropathy. Histological examination of the sural nerve revealed a nerve trunk with perineural soft tissue, with the nerve bundles being irregular and separated by fibrous tissue bands. The later reveals small perivascular infiltration of chronic inflammatory cells, and no granuloma or AFB is seen. The genetic test of whole exome screening for heriditatory neuropathy showed pathogenic (PM2, PVS, PP5) with a gene impact of (NF2: c.363+1G>T), which is a rare entity in our case study to consider the diagnosis despite negative family history. We highlight this rare disease in young man with a high index of clinical suspicion for its diagnosis. Bangladesh J Medicine 2024; 35: 101-105

Endothelial dysfunction of syphilis: Pathogenesis.

Treponema pallidum is the causative factor of syphilis, a sexually transmitted disease (STD) characterized by perivascular infiltration of inflammatory cells, vascular leakage, swelling and proliferation of endothelial cells (ECs). The endothelium lining blood and lymphatic vessels is a key barrier separating body fluids from host tissues and is a major target of T. pallidum. In this review, we focus on how T. pallidum establish intimate interactions with ECs, triggering endothelial dysfunction such as endothelial inflammation, abnormal repairment and damage of ECs. In addition, we summarize that migration and invasion of T. pallidum across vascular ECs may occur through two pathways. These two mechanisms of transendothelial migration are paracellular and cholesterol-dependent, respectively. Herein, clarifying the relationship between T. pallidum and endothelial dysfunction is of great significance to provide novel strategies for diagnosis and prevention of syphilis, and has a great potential prospect of clinical application.

A fatal case of fulminant group: a streptococcal infection in a neonate

BackgroundFulminant hemolytic streptococcal infection is a condition of sudden onset and rapidly progressing septic shock caused by Streptococcus pyogenes. It causes beta (complete) hemolysis. Although type A Streptococcus occurs more frequently, all streptococci that cause beta-hemolysis are eligible as causes. This report describes a rare autopsy case of fulminant group A streptococcal infection in a neonate.Case presentationA 16-day-old girl, 3300 g, born by spontaneous delivery at 41 weeks 1 day, experienced a 1-day history of low-grade fever, malaise, and a few hours of cyanosis and anuria, prompting her parents to bring her to the hospital. Her eldest brother, who lived with her, had been infected with Streptococcus approximately one month earlier, and had been treated with ten days of antibiotics. The infant died three hours after presentation. Autopsy findings indicated her to be 52 cm in length, weighing 3585 g, with medium build and normal nutrition. Her lungs were slightly oligemic with decreased volumes. The liver and kidneys were mildly enlarged. The spleen was markedly enlarged. The adrenal glands showed diffuse cortical hemorrhage (Fig. 1). There was some thymic atrophy (thymus weight 7.4 g, < 1 SD below the mean). Histopathological findings included chronic and neutrophilic infiltration of the tonsils and multiple septic emboli containing cocci in the lungs. Perivascular inflammatory cell infiltrates were observed in the lungs, myocardium, kidneys, adrenal glands, brain, meninges, and liver, with micro-necrotic changes in the kidneys and liver. Fibrin thrombi were observed in multiple renal glomeruli. Hemophagocytosis by macrophages was observed in the spleen, liver, lymph nodes, bone marrow, and adrenal glands. Immunostaining showed positive results for group A Streptococcus antibody in the tonsils, with bacterial masses. Blood cultures were positive for group A Streptococcus pyogenes.ConclusionsBecause of the lower respiratory tract infection and suspected sibling transmission, in addition to the adrenal hemorrhages, a diagnosis of fulminant sepsis with group A Streptococcus pyogenes with associated Waterhouse–Friderichsen syndrome was made.

Dermal Hypersensitivity Reaction to Semaglutide: Two Case Reports.

Glucagon-like peptide-1 (GLP-1) receptor agonists are a class of antidiabetic agents that work by inducing insulin secretion and inhibiting release of glucagon in a glucose-dependent manner. They are especially promising given their long duration of action, decreased risk of hypoglycemia, and added benefit of weight loss. Semaglutide is a GLP-1 receptor agonist that has been approved for type II diabetes and chronic weight management in obese adults. Cases of hypersensitivity reactions have been previously reported in patients taking GLP-1 receptor agonists dulaglutide and liraglutide. However, to our knowledge, there have been no reports of hypersensitivity reactions to semaglutide. Here, we present two cases of dermal hypersensitivity reactions in patients taking semaglutide for type II diabetes. In the first case, a 75-year-old woman who had been taking semaglutide for 10 months presented with an eruption on her legs, back, and chest for 3 months duration. Histology showed a subepidermal blister with eosinophils, suggestive of a drug hypersensitivity reaction. In the second case, a 74-year-old white man who had been taking semaglutide for 1 month presented with an eruption on the bilateral flanks and lower abdomen for 3 weeks duration. Histology revealed perivascular inflammatory cell infiltrate with eosinophils, also suggestive of a drug hypersensitivity reaction. Both patients began experiencing resolution of their symptoms within 1 month of discontinuing semaglutide. J Drugs Dermatol. 2023;22(4): doi:10.36849/JDD.6550 Citation: Ouellette S, Frias G, Shah R, et al. Dermal hypersensitivity reaction to semaglutide: Two case reports. J Drugs Dermatol. 2023;22(4):413-415. doi:10.36849/JDD.6550.

PS-B01-7: VASCULAR SMOOTH MUSCLE CELL NOX5 REGULATES FIBROBLAST PHENOTYPIC SWITCH AND CARDIOVASCULAR FIBROSIS

Objective: We previously observed that mice expressing human Nox5 (hNox5) in VSMC exhibit vascular dysfunction and cardio-renal fibrosis, where mechanisms are unknown. Here we postulated that VSMC-Nox5 promotes fibroblast phenotypic changes leading to myofibroblast differentiation and pro-fibrotic responses. Design and Methods: Fibroblasts were cultured from wildtype (WT) and hNOX5 mice (Nox5 + SM22 +). Mice (20 weeks old) were infused with Ang II (600 ng/Kg/day) for 28 days and renal fibrosis/inflammation studied. Markers of myofibroblasts, pro-fibrotic and inflammatory phenotypes were assessed by qPCR and immunoblotting. Results: Fibroblasts from Nox5 + SM22 + mice exhibited increased mRNA of pro-fibrotic markers, such as Col1A1 (2-ddC:1.74 ± 0.16 vs. WT 0.67 ± 0.11), Col3A1 (2-ddC:1.74 ± 0.18 vs. WT 0.96 ± 0.24) and TIMP3 (2-ddC:2.65 ± 0.25 vs. WT 0.38 ± 0.07), p &lt; 0.05. Myofibroblast phenotype (SMC) markers mRNA, aSMA (2-ddC:1.54 ± 0.05 vs. WT 0.78 ± 0.17) and Myocd (2-ddC:1.36 ± 0.17 vs. WT 0.39 ± 0.22) were also increased, p &lt; 0.05. mRNA expression of CD36 (2-ddC:1.37 ± 0.07 vs. WT 86 ± 0.24), TNFa (2-ddC:1.32 ± 0.2 vs. WT 0.71 ± 0.17) and TNFR1 (2-ddC:1.26 ± 0.04 vs. WT 1.02 ± 0.10) were increased, while CD68 expression was decreased (2-ddC:0.82 ± 0.11 vs. WT 1.36 ± 0.18) in fibroblasts from Nox5+SM22+ mice (p &lt; 0.05). In Nox5 mice fibroblasts, ROS production and TGFb protein expression (AU:1.8 ± 0.05 vs. WT 1.4 ± 0.06), as well as TGFbR2 gene expression (2-ddC:2.04 ± 0.17 vs. WT 0.57 ± 0.12), were increased (p &lt; 0.05). Kidneys from Ang II-infused Nox5+SM22+ mice exhibited significant perivascular fibrosis and inflammatory cell infiltration compared to WT. Kidney expression of vimentin (AU:1.01 ± 0.05 vs WT 0.85 ± 0.03) and aSMA (AU:0.44 ± 0.03 vs WT 0.33 ± 0.01), markers of myofibroblast differentiation, were increased in Nox5 mice (p &lt; 0.05). Gene expression of DNMT3a and TET2, DNA methylation regulatory enzymes, were also increased in fibroblasts from Nox5+SM22+ mice, p &lt; 0.05. Conclusion: VSMC-Nox5 regulates fibroblast phenotypic switch leading to fibrosis; a process that may involve increased production of ROS and TGFb, and activation of DNA methylation pathways.

Dermatomyositis Presenting with Isolated Dysphagia: A Case Report

We report a case of a 75-year-old woman who was diagnosed with dermatomyositis presenting with isolated dysphagia. There were no obvious cranial nerve deficits with normal motor grade in all the limbs in neurological examinations, but a suspicious rash was observed in the anterior chest. The serum creatine kinase was 306 IU/L, and active myopathic changes in bilateral limb muscles were observed in the electromyography test. Muscle biopsy from vastus lateralis showed perivascular infiltration of mononuclear inflammatory cells, which was compatible with dermatomyositis. She had responded to oral prednisolone and azathioprine.

Fingolimod attenuates ovalbumin-induced airway inflammation via inhibiting MAPK/ERK signaling in mice.

The current study was designed to investigate the potential anti-inflammatory and antioxidant effects of fingolimod against Ovalbumin (Ova)-induced allergic airway inflammation compared to dexamethasone. Fingolimod was given (0.5 mg/kg/day, p.o.) for sensitized mice 1 hbefore Ova challenge from Days 19 to 24. Fingolimod significantly inhibited Ova-induced elevation of inflammatory cells and eosinophils numbers in bronchoalveolar lavage fluid(BALF) and reduced concentrations of immunoglobulin E in serum and of sphingosine-1-phosphate, interleukin(IL)-4, and IL-13 in BALF. Fingolimod inhibited microvascular leakage and edema as reflected by the decreased lung/body weight index. These findings were supported by histopathological examination results showing that fingolimod substantially decreased perivascular edema and inflammatory cell infiltration. Fingolimod also attenuated Ova-induced oxidative stress as evidenced by decreased malondialdehyde concentration along with increasing concentrations of reduced glutathione and superoxide dismutase in lung tissues. Fingolimod also significantly decreased monocyte chemoattractant protein-1(MCP-1), p-ERK,and p-P38 in lung tissues of Ova-challenged mice. In conclusion, the current study demonstrated the anti-inflammatory and antioxidant effects of fingolimod in allergic airway inflammation that might be associated with the downregulation of mitogen activated kinases signaling to decrease T helper 2 cytokine secretion (IL-4 and IL-13) and MCP-1 expression, along with the inhibition of oxidative stress.

Obstacles in Diagnosing and Treating a Case of Primary Cutaneous CD8-Positive Aggressive Epidermotropic T-Cell Lymphoma; A Case Report

Cutaneous T-cell lymphomas (CTCL) have a wide spectrum of clinical, histological, immunophenotypic features and genetic alterations which make their diagnosis challenging. Due to the rarity and poor characterization of Primary cutaneous CD8-positive aggressive epidermotropic T-cell lymphoma ((PCAECyTCL), it remains a provisional entity in WHO classification (2018) (1). The constant immunohistochemical finding in PCEACyTCL is CD8 +/ CD4 - expression that is non-specific. So, it needs a consensus on the correlation of clinical & lab for accurate diagnosis (2).In addition to the aggressive presentation of the disease and the associated burden of infection make treatment decisions very challenging. Herein, we are presenting our experience in treating an aggressive case of PCEACyTCL, and how we dealt with the disease and its complications. a 58-year-old male, with a history of Psoriasis, started with him 30 years and he was on topical treatment for it. Referred to us after 3 months journey in the Dermatological department with rapidly progressive maculopapular lesions & tumors, showing central ulcerations, necrosis, and complicated by purulent bacterial infection involving his face, scalp, neck, all 4 limbs, whole trunk, perineum with the oral cavity and oropharynx. There was also generalized lymphadenopathy (Figure 1). His lab results were within the normal range with no evidence of any abnormal infiltration by lymphocytes in peripheral blood and Bone marrow examination. Punch skin biopsy showed that the dermis was the seat of dense localized upper & mid dermal wedge-shaped angiocentric & perivascular inflammatory cell infiltrate composed mainly of activated lymphocytes mixed with histiocytes, plasma cells & neutrophils with atypical, transformed lymphocytes. The infiltrate is encroaching upon the epidermis with degeneration of the basal cell layer & epidermotropism. The Immunohistochemistry revealed diffuse positivity of CD3, weak positivity of CD4, and strong positivity of CD8 with negativity for CD7, CD20, CD30, and ALK in the atypical, transformed T-lymphocytes (Figure 2). The patient was diagnosed to have pcAECyTCL. The staging was done using Contrast CT of the chest, abdomen, and pelvis and showed generalized lymphadenopathy with pulmonary nodules, so he was staged (IVB). After mild improvement of the patient's general condition by anti-biotics, painkillers, and supportive treatment, he started CHOP/Etoposide (doxorubicin 50 mg/m2, cyclophosphamide 750 mg/m2, and vincristine 1.4 mg/m2 by intravenous infusion on day 1, etoposide 100 mg/m2 intravenously days 1-3) to be repeated/3 weeks, with G-CSF as our patient showed aggressive myelosuppression after cycles. There was a very promising improvement in his skin lesions (Figure 3), oral ulcers, and general condition. After 3 cycles of chemotherapy, a PET scan showed: Non metabolically active lymphadenopathy. Metabolically active diffuse skin lesions forming irregular skin thickening over the trunk & limbs (SUV max 5). So, he continued further 3 cycles with preparation for an ASCT. Unfortunately, before stem cell transplantation, the skin lesions progressed again with the same aggression. So, he was given 1 cycle of GEMOX (Gemcitabine1 gm/m2 and Oxaliplatin 100 mg/m2 to be repeated/14 days) then he got COVID-19 infection and is still under treatment for it. In our patient, psoriasis can be considered a susceptible predisposing factor for pcAECyTCL according to the proposed theory by Cai, Fleming and Yan, and others (3,4). One of the obvious problems of pcAECyTCL is the exhibition of T-helper-1 cytokine profile, this makes many treatment options inappropriate as Interferons (5). Theoretically, multi-agent chemotherapies appear to be better options, but they carry the risk of toxicity and myelosuppression, and their response is unsatisfactory till now. There are emerging novel therapies but still not applied to this type of lymphoma due to its rarity (6, 7, 8). Bastidas et al. was suggesting that Ruxolitinib may play a future role in its treatment, but this is still in need of future research (9). The CHOP/etoposide protocol was promising in our patient, but it didn't give a durable response. The plan after improvement from COVID-19 infection is to give a targeted therapy as Brentuximab if available or an aggressive protocol as Hyper-CVAD followed by ASCT hoping for CR, longer OS, and better quality of life. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Abstract 14566: The Role of Eosinophils in Pulmonary Hypertension

Introduction: Pulmonary hypertension (PH) is a severe life-threatening disease with insidious onset and high mortality, featured by pulmonary vascular remodeling and perivascular inflammatory cell infiltration. However, the precise immune mechanisms underlying PH remain unclear. Although an enhanced Th2 immune response in PH has been reported for years, the role of eosinophils (EOS), one of the Th2 effector cells, in PH is seldom reported. Investigating the roles and molecular mechanisms of EOS may present a novel paradigm of PH development. Hypothesis: EOS protect against PH through lipid metabolites. Methods: EOS infiltration and chemotaxis were investigated in peripheral blood and lung tissues from PH patients and sugen/hypoxia-induced PH mice. ΔdblGATA mice and anti-IL5 antibody (TRFK5)-treated mice were applied to investigate the role of EOS in PH development. Flow cytometry-based assays were used to quantify infiltration of different immune cells. The culture supernatants and lysates of EOS were collected to explore the mechanisms in co-culture cell experiments. Results: EOS accumulated in lung tissues from PH patients and mice, and the infiltration of EOS into pulmonary tissues during PH may be promoted by fibroblast-derived CCL11. Furthermore, EOS deficiency increased neutrophil (p=0.0038) and monocyte/macrophage (p=0.0344) infiltration and promoted pulmonary arterial smooth muscle cell proliferation, leading to aggravated PH in mice. Mechanistically, arachidonate 15-lipoxygenase (ALOX15), which catalyzes the production of pro-resolving lipid mediators, is specifically expressed by EOS. Conclusions: EOS play a beneficial role during PH development via ALOX15 and its downstream lipid mediators, suppressing perivascular inflammation and maintaining smooth muscle cell homeostasis.

The role of calcium-sensitive receptor in ovalbumin-induced airway inflammation and hyperresponsiveness in juvenile mice with asthma.

The role of the calcium-sensitive receptor (CaSR) was assessed in a juvenile mouse model of asthma induced by ovalbumin (OVA). The experiment was divided into normal control, OVA, and OVA +2.5/5mg/kg NPS2143 (a CaSR antagonist) groups. OVA induction was performed in all groups except the normal control, followed by assessing airway hyperresponsiveness (AHR) and lung pathological changes. Serum OVA-specific IgE and IgG1 were detected with an enzyme-linked immunosorbent assay (ELISA), and inflammatory cells were counted in bronchoalveolar lavage fluid (BALF). Real-time quantitative polymerase chain reaction, ELISA, and western blotting were performed to detect gene and protein expression. NPS2143 improved the OVA-induced AHR in mice, and AHR was higher in the OVA +2.5mg/kg NPS2143 group than in the OVA +5mg/kg NPS2143 group. Furthermore, NPS2143 reduced the production of OVA-specific IgE and IgG1 in serum and the number of eosinophils and lymphocytes in BALF in OVA mice with reduced CaSR expression in lung tissues. Besides, OVA-induced mice exhibited peribronchial and perivascular inflammatory cell infiltration, which was accompanied by severe goblet cell hyperplasia/hyperplasia and airway mucus hypersecretion. Furthermore, these mice exhibited increased levels of Interleukin (IL)-5, IL-13, MCP-1, and eotaxin, which were alleviated by NPS2143. The 5mg/kg NPS2143 showed more effective than the 2.5mg/kg treatment. CaSR expression was elevated in the lung tissues of OVA-induced asthmatic juvenile mice, whereas the CaSR antagonist NPS2143 reduced AHR and attenuated the inflammatory response in OVA-induced juvenile mice, possibly exerting therapeutic effects on childhood asthma.

Lung cancer surgery after COVID-19 infection in a patient with severe interstitial pneumonia and restrictive ventilatory impairment

BackgroundThe spread of COVID-19 infection increased the number of patients who underwent pulmonary resection for lung cancer after COVID-19 infection. It is unclear how previous infection with COVID-19 affects perioperative complications and acute exacerbation of interstitial pneumonia after surgery in patients with interstitial pneumonia.Case presentationAn 80-year-old man was referred to our hospital because of a tumor in his left lung. Chest computed tomography showed a 28-mm nodule in the lower lobe of the left lung and usual interstitial pneumonia in bilateral lungs. Bronchoscopic examination was performed, which diagnosed squamous cell carcinoma. Pulmonary function testing revealed restrictive ventilatory impairment, and we planned to perform basal segmentectomy of the left lung. However, before the planned surgery, the patient contracted symptomatic COVID-19. Chest computed tomography revealed ground-glass opacities owing to COVID-19. The patient was admitted for surgery 7 weeks after COVID-19 infection. Preoperatively, pulmonary function testing was repeated, which revealed decreased % vital capacity (%VC) and % diffusing capacity for carbon monoxide (%DLco). The 6-min walk test indicated a distance of 500 m, and the percutaneous oxygen saturation at the end of the test was 94%. Basal segmentectomy of the left lung was performed by video-assisted thoracoscopic surgery. The patient’s postoperative course was favorable, and he was discharged without the need for oxygen inhalational therapy 12 days after the surgery. Pathological examination of the resected specimen revealed usual interstitial pneumonia in the non-cancerous areas of the lung. Additionally, the infiltration of immature fibroblasts in the alveoli and perivascular infiltration of inflammatory cells were observed, which were consistent with fibrotic change after inflammation owing to COVID-19. Three months after the surgery, the patient was alive without recurrence or acute exacerbation of the interstitial pneumonia. Pulmonary function testing 6 weeks after surgery revealed decreased %VC and %DLco. Testing 12 weeks after surgery revealed persistently decreased %VC and improved %DLco (Table 1).Table 1Pulmonary function test results before and after COVID-19 infection and 6 and 12 weeks after surgeryVC (ml)%VC (%)%DLco (%)Before COVID-19 infection207071.974.97 weeks after COVID-19 infection170059.651.96 weeks after surgery150052.653.112 weeks after surgery151053.061.7%VC % vital capacity, %DLco % diffusing capacity for carbon monoxideConclusionWe successfully performed basal segmentectomy of the left lung for lung cancer 7 weeks after COVID-19 infection in a patient with severe interstitial pneumonia and restrictive ventilatory impairment.

Abstract 127: Nox5 Expression In A Vascular Smooth Muscle Cell-specific Manner Induces Fibroblast To Myofibroblast Differentiation

Mice expressing human Nox5 (hNox5) in VSMC exhibit cardfiovascular fibrosis, where mechanisms are unknown. We postulated that VSMC-Nox5 promotes fibroblast to myofibroblast differentiation that contributes to fibrosis. Fibroblasts were cultured from wildtype (WT) and hNOX5 mice. Mice (20 weeks old) were infused with Ang II (600 ng/Kg/day) for 28 days and renal fibrosis/inflammation studied. Markers of myofibroblasts (αSMA), and pro-fibrotic and inflammatory signaling molecules were assessed by qPCR and immunoblotting. Inflammatory infiltrate was assessed by FACS. Fibroblasts from Nox5 mice exhibited increased mRNA of markers of myofibroblast αSMA (2 -ddC :1.54±0.05 vs. WT 0.78±0.17) and Myocd (2 -ddC :1.36±0.17 vs. WT 0.39±0.22), as well as, pro-fibrotic markers, Col1A1 (2 -ddC :1.74±0.16 vs. WT 0.67±0.11), Col3A1 (2 -ddC :1.74±0.18 vs. WT 0.96±0.24) and TIMP3 (2 -ddC :2.65±0.25 vs. WT 0.38±0.07), p&lt;0.05. mRNA expression of CD36 (2 -ddC :1.37±0.07 vs. WT 86±0.24), TNFα (2 -ddC :1.32±0.2 vs. WT 0.71±0.17) and TNFR1 (2 -ddC :1.26±0.04 vs. WT 1.02±0.10) were increased, while CD68 expression was decreased (2 -ddC :0.82±0.11 vs. WT 1.36±0.18) in fibroblasts from Nox5 mice (p&lt;0.05). In Nox5 mice fibroblasts, ROS production and TGFβ protein expression (AU:1.8±0.05 vs. WT 1.4±0.06), as well as TGFβR2 gene expression (2 -ddC :2.04±0.17 vs. WT 0.57±0.12), were increased (p&lt;0.05). mRNA of DNMT3a and TET2, DNA methylation regulatory enzymes, were also increased in fibroblasts from Nox5 mice, p&lt;0.05. Kidneys from Ang II-infused Nox5 mice exhibited significant perivascular fibrosis and inflammatory cell infiltration compared to WT, as well as increased protein expression of TGFβ (AU: 3.59±0.8 vs. WT 1.54±0.2) and IL-11 (AU: 0.64±0.08 vs. WT 0.39±0.04), p&lt;0.05; where levels of macrophage F4/80+ cells (%:24±2 vs WT 18±1, p&lt;0.05) and levels of cytotoxic CD8+ T cells were increased, p&lt;0.05. Kidney expression of vimentin (AU:1.01±0.05 vs WT 0.85±0.03) and αSMA (AU:0.44±0.03 vs WT 0.33±0.01), were increased in Nox5 mice (p&lt;0.05). Nox5 regulates fibrosis by inducing fibroblast-to-myofibroblast differentiation, possibly through increased ROS. These processes may be important in Nox5-assocated cardiovascular-renal fibrosis.

Cyclic Targetoid Rash With Menstruation

A 41-year-old woman had a 5-year history of targetoid purpuric-red plaques on the legs at a menstrual cycle interval. The eruption predictably started 5 to 7 days before menstruation and resolved within several days after cessation of menses. She had no history of menstrual irregularity or other comorbidities. There was no history of intake of exogenous progesterone. On physical examination, there were multiple targetoid plaques with purpuric-red color on the leg (Figure 1). Skin specimen showed parakeratosis, spongiotic microvesicle, upper dermal edema, and perivascular infiltration of inflammatory cells (Figure 2).

The coincidence of psoriasis vulgaris and pemphigus foliaceous in geriatric after COVID-19 vaccination

Background: Psoriasis is a chronic autoimmune disease characterized by well-demarcated, erythematous, scaly plaques, such as mica. Psoriasis occurs as a damaging result of Th17, TNF-α, and IFN-γ cells. The coincidence of psoriasis with pemphigus foliaceous is rare. Several studies have shown that Th17, TNF-α, and IFN-γ cells induced by COVID-19 vaccination can play a role in this mechanism although it remains unclear. Case series: A 60-year-old woman without comorbidities with a 6-year history of controlled psoriasis, since 2016, with the administration of methotrexate and phototherapy. The diagnosis of psoriasis is clinically based on the form of erythematous, scaly plaques scattered throughout the body. The patient got the COVID-19 vaccination twice during the pandemic, followed by the exacerbation of psoriasis and coincidence with pemphigus foliaceus. The biopsy showed epidermal acantholysis with perivascular infiltration of PMN inflammatory cells and lymphocytes. The patient did not improve with the administration of methotrexate and phototherapy but showed improvement with methylprednisolone injections with tapering. Psoriasis relapsed again, but the patient improved after being given 4 times injections of secukinumab. Conclusion: COVID-19 vaccination is necessary during a pandemic, but can lead to post-vaccination autoimmune exacerbations, such as the coincidence of psoriasis and pemphigus foliaceus. More research is needed to understand the potential of COVID-19 vaccination which is the first mRNA vaccine in humans.

Wenyang Huazhuo Tongluo formula alleviates pulmonary vascular injury and downregulates HIF-1α in bleomycin-induced systemic sclerosis mouse model

BackgroundVascular damage, autoimmune abnormalities, and fibrosis are the three pathological features of systemic sclerosis (SSc).However, pulmonary vascular damage is the main factor affecting the progression and prognosis of SSc. The main purpose of this study was to explore the molecular mechanism of Wenyang Huazhuo Tongluo Formula in alleviating pulmonary vascular injury in bleomycin-induced SSc mouse model.MethodsMasson staining and H&E staining were used to analyze the degree of pulmonary vascular fibrosis and the infiltration of leukocyte cells in lung tissue ofbleomycin-induced SSc mouse models treated with saline (BLM group), Wenyang Huazhuo Tongluo Formula (WYHZTL group) and HIF-1α inhibitor KC7F2 (KC7F2 group). Blood vessel exudation was determined by analyzing the cell number and albumin concentration in bronchoalveolar lavage fluid using a cell counter and ELISA assay, respectively. The degree of vascular injury was assessed by measuring the expression levels of vWF, E-selectin, ICAM-1, VCAM-1, VE-cadherin and claudin-5 in serum and pulmonary vascular endothelial cells using ELISA and immunofluorescence staining. Finally, the effect of Wenyang Huazhuo Tongluo Formula on the expression of HIF-1α was detected using immunofluorescence staining.ResultsWenyang Huazhuo Tongluo Formula and KC7F2 significantly inhibited bleomycin-induced pulmonary vascular fibrosis and the level of perivascular inflammatory cell infiltration. The number of cells and the concentration of albumin were significantly reduced in the bronchoalveolar lavage fluid of the WYHZTL group and KC7F2 group compared with the BLM group. In addition, treatment with Wenyang Huazhuo Tongluo Formula and KC7F2 significantly downregulated the expression levels of vWF, E-selectin, ICAM-1, VCAM-1 and HIF-1α, but upregulated the expression of VE-cadherin and claudin-5 in serum and pulmonary vascular endothelial cells, compared with treatment with saline.ConclusionsThis study reveals that Wenyang Huazhuo Tongluo Formula plays a new role in the treatment of SSc by alleviating pulmonary vascular damage. Furthermore, we found that Wenyang Huazhuo Tongluo Formula alleviates pulmonary vascular injury and inhibits HIF-1α expression.

Bullous systemic lupus erythematosus with nephrotic syndrome in an adolescent girl: a case report

Bullous systemic lupus erythematosus is an uncommon autoimmune subepidermal vesiculobullous disease occurring in less than 5% of patients with systemic lupus erythematosus. The diagnosis of bullous systemic lupus erythematosus is based on clinical picture, histopathological findings, direct immunofluorescence and other immunologic tests. Importantly, establishing the diagnosis of bullous systemic lupus erythematosus requires the occurrence of systemic lupus erythematosus according to the American College of Rheumatology criteria. We report a case of bullous systemic lupus erythematosus in a 16-year-old Vietnamese girl, who demonstrated an acquired vesiculobullous eruption associated with nephrotic syndrome and fulfilled the European League Against Rheumatism/ American College of Rheumatology 2019 classification criteria of systemic lupus erythematosus. Clinical examination showed numerous tense, clear fluid-filled vesicles and bullae affecting the whole body with the predilection for the face, neck, chest, abdomen and bilateral inner thigh areas. Erosions were observed on the tongue and the buccal mucosa. Histopathologic examination showed subepidermal vesicle containing abundant neutrophils and perivascular mixed inflammatory cell infiltration. Microabscesses at tips of dermal papillae and the features of a leukocytoclastic vasculitis were not seen. Direct immunofluorescence of perilesional skin biopsies demonstrated linear deposition of IgG, IgA, IgM and C3 in the basement membrane zone. Linear immunoglobulin deposition displayed a u-serrated pattern with the predominant staining intensity of IgG. Serologic tests showed positive antinuclear antibody. Complement components assay revealed low levels of C3 (66.5 mg/dL) and C4 (3,9mg/dL). Proteinuria level was increased to 3.5g/24 hours. The final diagnosis of bullous systemic lupus erythematosus with nephrotic syndrome was made. The patient was treated with a high-dose oral glucocorticoid scheme and showed significant clinical improvement.

NOX5 EXPRESSION IN A VASCULAR SMOOTH MUSCLE CELL-SPECIFIC MANNER INDUCES FIBROBLAST PHENOTYPIC SWITCH AND PRO-FIBROTIC EFFECTS

Objective: Mice expressing human Nox5 (hNox5) in vascular smooth muscle cells (VSMC) exhibit redox-sensitive vascular dysfunction and cardio-renal fibrosis. Mechanisms underlying pro-fibrotic effects are unclear. Here we assessed whether hNox5 in VSMCs promotes fibroblast phenotypic changes leading to myofibroblast differentiation and pro-fibrotic/inflammatory responses. Design and method: Fibroblasts were cultured from wildtype (WT) and mice expressing hNOX5 in VSMC (Nox5+SM22+). Mice (20 weeks old) were infused with Ang II (600 ng/Kg/day) for 28 days and renal fibrosis/inflammation studied. Markers of myofibroblasts, pro-fibrotic and inflammatory phenotypes were assessed by qPCR and immunoblotting. Inflammatory infiltrate was assessed by FACS. Results: Fibroblasts isolated from Nox5+SM22+ mice exhibited increased mRNA expression of pro-fibrotic markers, such as Col1A1 (2-ddCt: 1.74 ± 0.16 vs. WT 0.67 ± 0.11), Col3A1 (2-ddCt: 1.74 ± 0.18 vs. WT 0.96 ± 0.24) and TIMP3 (2-ddCt: 2.65 ± 0.25 vs. WT 0.38 ± 0.07), p &lt; 0.05. Myofibroblast phenotype (SMC) markers mRNA, aSMA (2-ddCt: 1.54 ± 0.05 vs. WT 0.78 ± 0.17) and Myocd (2-ddCt: 1.36 ± 0.17 vs. WT 0.39 ± 0.22) were also increased in fibroblasts from Nox5 mice, p &lt; 0.05. In terms of inflammatory phenotype, we observed that mRNA expression of CD36 (2-ddCt: 1.37 ± 0.07 vs. WT 86 ± 0.24), TNFa (2-ddCt: 1.32 ± 0.2 vs. WT 0.71 ± 0.17) and TNFR1 (2-ddCt: 1.26 ± 0.04 vs. WT 1.02 ± 0.10) were increased, while CD68 expression was decreased (2-ddCt: 0.82 ± 0.11 vs. WT 1.36 ± 0.18) in fibroblasts from Nox5+SM22+ mice (p &lt; 0.05). In Nox5 mice fibroblasts, key regulators of fibrosis such as ROS production and TGFb protein expression (AU: 1.8 ± 0.05 vs. WT 1.4 ± 0.06), as well as TGFbR2 gene expression (2-ddCt: 2.04 ± 0.17 vs. WT 0.57 ± 0.12), were increased (p &lt; 0.05). Kidneys from Ang II-infused Nox5+SM22+ mice exhibited significant perivascular fibrosis and inflammatory cell infiltration compared to WT. Kidney expression of vimentin (AU: 1.01 ± 0.05 vs WT 0.85 ± 0.03) and aSMA (AU: 0.44 ± 0.03 vs WT 0.33 ± 0.01), markers of myofibroblast differentiation, were increased in Nox5 mice (p &lt; 0.05). In kidneys from Nox5+SM22+ mice, increased frequencies of macrophage F4/80 + (%: 24 ± 2 vs WT 18 ± 1, p &lt; 0.05). Conclusions: Our findings suggest that Nox5 in VSMCs influences fibroblast phenotypic switching to myofibroblasts that likely influences cardiovascular and renal fibrosis in hypertension.

Effects of YM155 on the proliferation and apoptosis of pulmonary artery smooth muscle cells in a rat model of high pulmonary blood flow-induced pulmonary arterial hypertension

ABSTRACT Introduction Proliferation and apoptosis of pulmonary artery smooth muscle cells (PASMCs) play an important role in the occurrence and development of pulmonary arterial hypertension (PAH). The purpose of this study was to investigate the effects of survivin inhibitor YM155 on the proliferation and apoptosis of PASMCs in rats with PAH induced by high pulmonary blood flow. Methods Thirty male Sprague-Dawley (SD) rats were randomly divided into control, model, and YM155 intervention groups. A rat model of PAH induced by high pulmonary blood flow was established, and it was confirmed by assessments of right-ventricular pressure (RVP) and right ventricular hypertrophy index (RVHI). Immunohistochemical staining and western blot analysis were used to detect the expression of survivin, and the proliferation and apoptosis of PASMCs. Lastly, the effects of in vivo treatment of YM155 were tested. Results The increased expression of survivin mRNA and protein were observed in the model group, accompanied by pulmonary arteriolar wall thickening, lumen stenosis, and perivascular inflammatory cell infiltration. Elevated expression of survivin and pulmonary vascular remodeling were significantly mitigated after YM155 treatment. Specifically, the YM155 intervention group had a significantly lower PASMC proliferation rate and a higher PASMC apoptotic rate. Conclusion YM155 suppressed PASMC proliferation and promoted PASMC apoptosis by inhibiting survivin expression and thereby reducing pulmonary vascular remodeling in high pulmonary blood flow-induced PAH in vivo.

Norfloxacin-Repeated Dose Toxicity on Liver of Broiler Chickens

Background: Norfloxacin is a second generation fluoroquinolone, primarily used in the treatment of urinary tract infections. However, later clinical studies have documented the efficacy of norfloxacin for a variety of Gram-negative infections including pneumonia, CNS/CSF infections, prostatitis and septicemia. The present study was conducted to investigate the toxic effect of norfloxacin during 28 day repeated dose toxicity on the liver tissue of broiler chickens. Materials and Methods: The experimental birds acclimatized to laboratory housing condition were assigned as vehicle, control, treatment, and satellite groups (each group contained 6 birds). Stellate group, without administering Norfloxacin solution with partial control group was maintained for extra two weeks after the 28-day period. Findings: Gross lesions in the liver of group IV and V observed were fatty change, enlargement, and increase of size and petechial hemorrhagic. Hepatocytes were swollen with mild vacuolar changes with granular cytoplasm. Focal areas of hepatocytes with degeneration infiltration of mononuclear cells, dilation of sinusoid, perivascular infiltration of inflammatory cells, bile duct epithelial hyperplasia and perivascular infiltration were noticed in the present study. The organ/body weight ratio percentages of liver for groups I, II, III, IV and V on 29th day were 2.81, 3.53, 3.54, 3.98 and 5.03 respectively. There was significant (P&lt;0.001) increase in organ/body weight percentage ratio of group V as compared to the control group. On day 21 of treatment the serum ALT concentration was significantly increase in group V (P &lt; 0.001) when compared to group I birds. On day 28 of treatment the mean serum ALT concentration was significantly (P &lt; 0.01) higher in group V birds compared to group I birds. On 21st day of treatment the serum AST level of group V was significantly increased (P &lt; 0.001) when compared to group I birds. On 28th day of treatment the mean serum AST was significantly high in-group V (P &lt; 0.001) birds when compared to group I birds. These findings were accordance with finding of other authors. Conclusion: According to gross pathology, histopathology and biochemical findings in the present study it was concluded that the norfloxacin has toxic effect on the liver tissue of chickens at the dose of 333 and 1100 mg/kg orally.

Steroid-resistant Acute Generalized Exanthematous Pustulosis Mimicking Generalized Pustular Psoriasis Successfully Treated by Methotrexate

Acute generalized exanthematous pustulosis is a rare drug-induced eruption that is characterized by sterile non-follicular pustules arising on an often edematous diffuse erythematous background. Generalized pustular psoriasis is an acute and severe clinical form of psoriasis presenting as pustular eruption with erythematous base. Differentiating both diseases is often challenging because of their clinical and histopathological similarities. A 62-year-old woman presented with pustular eruption and fever three days after taking propyphenazone. Laboratory findings revealed leukocytosis and neutrophilia. Histopathological findings revealed a subcorneal spongiform pustule filled with neutrophils and perivascular inflammatory cell infiltration with neutrophils in the dermis. She was initially treated with systemic steroids, however, the lesions showed insignificant improvement. Treatment was then shifted to methotrexate which resulted in a dramatic clinical improvement.